PMID- 27531309
OWN - NLM
STAT- MEDLINE
DCOM- 20170512
LR  - 20171215
IS  - 1873-3468 (Electronic)
IS  - 0014-5793 (Linking)
VI  - 590
IP  - 18
DP  - 2016 Sep
TI  - Extracellular pH regulates autophagy via the AMPK-ULK1 pathway in rat 
      cardiomyocytes.
PG  - 3202-12
LID - 10.1002/1873-3468.12359 [doi]
AB  - Various pathological conditions contribute to pH fluctuations and affect the 
      functions of vital organs such as the heart. In this study, we show that in rat 
      cardiomyocytes, acidic extracellular pH (pHe) inhibits autophagy, whereas 
      alkaline pHe stimulates it. We also find that adenosine monophosphate-activated 
      protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Unc-51-like 
      kinase 1 (ULK1) are very sensitive to pHe changes. Furthermore, by interfering 
      with AMPK, mTOR or ULK1 activity, we demonstrate that the AMPK-ULK1 pathway, but 
      not the mTOR pathway, plays a crucial role on pHe-regulated autophagy and 
      cardiomyocyte viability. These data provide a potential therapeutic strategy 
      against cardiomyocyte injury triggered by pH fluctuations.
CI  - (c) 2016 Federation of European Biochemical Societies.
FAU - Zhao, Liping
AU  - Zhao L
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Cui, Lin
AU  - Cui L
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Jiang, Xupin
AU  - Jiang X
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhang, Junhui
AU  - Zhang J
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhu, Minghua
AU  - Zhu M
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Jia, Jiezhi
AU  - Jia J
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhang, Qiong
AU  - Zhang Q
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhang, Jiaping
AU  - Zhang J
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhang, Dongxia
AU  - Zhang D
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China. 
      dxzhangswh@163.com.
FAU - Huang, Yuesheng
AU  - Huang Y
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing, China. 
      yshuangtmmu@163.com.
LA  - eng
PT  - Letter
PT  - Research Support, Non-U.S. Gov't
DEP - 20160901
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Protons)
RN  - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
RN  - EC 2.7.11.1 (ULK1 protein, rat)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - *Autophagy
MH  - Autophagy-Related Protein-1 Homolog/*metabolism
MH  - Cells, Cultured
MH  - Extracellular Space/*chemistry
MH  - Hydrogen-Ion Concentration
MH  - Myocytes, Cardiac/*metabolism
MH  - *Protons
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
OTO - NOTNLM
OT  - Unc-51-like kinase 1
OT  - adenosine monophosphate-activated protein kinase
OT  - autophagy
OT  - cardiomyocytes
OT  - pH
EDAT- 2016/08/18 06:00
MHDA- 2017/05/13 06:00
CRDT- 2016/08/18 06:00
PHST- 2016/04/18 00:00 [received]
PHST- 2016/08/02 00:00 [revised]
PHST- 2016/08/10 00:00 [accepted]
PHST- 2016/08/18 06:00 [entrez]
PHST- 2016/08/18 06:00 [pubmed]
PHST- 2017/05/13 06:00 [medline]
AID - 10.1002/1873-3468.12359 [doi]
PST - ppublish
SO  - FEBS Lett. 2016 Sep;590(18):3202-12. doi: 10.1002/1873-3468.12359. Epub 2016 Sep 
      1.